Biomedical subjects

M J Peach

Publications and source records attributed to M J Peach.

At least 55 records · Page 3Linked to original sources

PubMed1990

Role of atrial natriuretic peptide in the response to blood volume expansion in the weanling rat.

After acute blood volume expansion (BVE) in the rat, diuresis and natriuresis are reported to be minimal in rats 20 to 30 d of age, but increase to mature levels by 40 d of age. To evaluate the role of atrial natriuretic peptide (ANP) and its renal action in BVE, anesthetized Sprague-Dawley rats were studied at 25 to 30 (group I) and 45 to 50 d of age (group II). Hematocrit, mean arterial pressure, glomerular filtration rate, urine flow rate, urine sodium excretion, urine cyclic GMP excretion, and plasma ANP concentration [( ANP]) were measured before and after infusion of donor littermate whole blood, 2.5% body wt (BVE), and in time controls (no BVE) in each group. Baseline hematocrit, mean arterial pressure, and glomerular filtration rate were greater in group II than group I, but urine flow rate, urine sodium excretion, urine cyclic GMP excretion, and [ANP] did not differ. BVE caused a prompt increase in urine flow rate, urine sodium excretion, and [ANP], but not urine cyclic GMP excretion, in both groups, but there was no difference in the response between groups. Additional groups of rats of the same ages as groups I and II studied using a protocol similar to that of a previous report also showed the "mature" diuretic and natriuretic response even in the younger animals. We conclude that there is no further maturation of the renal response to acute BVE in the euvolemic rat after 25 d of age. The increase in [ANP] after acute BVE in the immature weanling rat is consistent with a role for ANP in mediation of the renal response.

Aging↗

PubMed1990

Molecular biology of the renal renin-angiotensin system.

This paper describes an interrelated series of studies designed to examine molecular and cellular aspects of renin expression and release within the kidney. Using immunocytochemical techniques, Northern blot analysis, in situ hybridization, measurement of renin activity, and the reverse hemolytic plaque assay, it has been possible to demonstrate that the intrarenal distribution of renin, renin gene expressing cells and the number of renin secretory cells vary during diverse physiologic and pathologic conditions. Overall, these studies demonstrate that the renal preglomerular vasculature has the plasticity and capacity to elicit a recruitment of renin containing and/or renin gene expressing cells.

Animals↗

PubMed1990

Comparison of spectrophotometric and biological assays for nitric oxide (NO) and endothelium-derived relaxing factor (EDRF): nonspecificity of the diazotization reaction for NO and failure to detect EDRF.

Endothelium-derived relaxing factor has been tentatively identified as nitric oxide (NO) partially on the basis of chemical assays. In the present study, saline solutions that were either bubbled continuously for 30 min with NO (NO/X) or prepared using 25 ml of NO/ml (NO/25) produced equivalent relaxations of segments of rabbit aorta which had the endothelium removed. NO solutions prepared using 0.1 ml of NO/ml (NO/0.1), and 3 mM sodium nitrite (NO2-) were significantly (P less than .05) less potent vasodilators than NO/X and NO/25 (order of potency: NO/X = NO/25 greater than NO/0.1 greater than NO2-). A novel automated method was developed to monitor nitrogen oxides using continuous-flow spectrophotometric detection (diazotization reaction). The absorbance readings for the solutions were NO/X greater than NO/25 = NO/0.1 = NO2-. Argon purging of NO/X, NO/25 and NO/0.1 solutions significantly (P less than .05) reduced (44-100%) the bioactivity of these solutions in inverse proportion to the initial volume of NO used in their preparation. In contrast, the absorbance values were unchanged, indicating that the chemical assay was not correlated with the bioassay. Varying the duration of NO gassing (1-30 min) significantly (P less than .05) increased the absorbance values, while having no effect on the vascular relaxations, elicited by the solutions. The diazotization assay did not detect nitrogen oxides released from cultured endothelial cells by bradykinin, ATP, or A23187, whereas the bioassay readily detected endothelium-derived relaxing factor release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Endothelium-dependent potentiation of human platelet aggregation.

The endothelium produces many substances which have the potential to alter hemostasis. We examined the influence of a substance(s) released by cultured bovine aortic endothelial cells on very early events (less than 5 sec) in platelet function, using a new quenched-flow approach. Contributions of the endothelial cell surface to alterations in platelet function were avoided by separating the endothelium and platelets. Superfusates from endothelial cells were allowed to interact with platelets for several seconds, followed by challenge with ADP to induce aggregation. Single-particle counting provided a sensitive index of aggregation kinetics. In this system, unstimulated endothelial-cell superfusate had no effect on aggregation induced by ADP. Stimulation of the endothelial cells with bradykinin produced an unstable factor(s) that potentiated ADP-induced platelet aggregation, was not affected by hemoglobin or cyclooxygenase inhibitions, and had no platelet aggregatory activity on its own. Nitric oxide inhibited aggregation and its effect was blocked by hemoglobin. The identity of the potentiating factor is unknown, but it does not appear to be platelet activating factor, thrombin, ADP, thromboxane, nitric oxide, or endothelium-derived relaxing factor.

Adenosine Diphosphate↗

PubMed1989

Indirect evidence for separate vesicular neuronal origins of norepinephrine and ATP in the rabbit vas deferens.

Various modulators of neurotransmission were examined for selective effects on the non-adrenergic or adrenergic components of neurotransmission in the vas deferens to test the hypothesis that ATP and norepinephrine are secreted from the same vesicles. The ATP receptor antagonist, arylazido aminopropionyl ATP (ANAPP), selectively depressed the non-adrenergic contraction and prazosin selectively depressed the adrenergic contraction in response to electrical stimulation. These results are consistent with the presence of two neurotransmitters, ATP and norepinephrine, which mediate neurogenic contractions. Prostaglandin E2 inhibited non-adrenergic, but enhanced adrenergic, electrically induced (10 Hz) contractions, presumably via a prejunctional mechanism. The adrenergic component of the neurogenic response was significantly more sensitive to treatment with guanethidine, guanabenz, and 6-hydroxy-dopamine. These results with a variety of agents are inconsistent with the hypothesis that the neurotransmitters. ATP and norepinephrine, are released in tandem from the same neuronal granules.

Adenosine Triphosphate↗

PubMed1989

Combined intrarenal renin-angiotensin blockade alters renal function and this is reversed by angiotensin II.

All the components of the renin-angiotensin system are present within the kidney and intrarenal effects have been demonstrated. We have previously shown that intrarenally confined doses of angiotensin II (Ang II) decreased renal excretory and haemodynamic function. In the present study we investigated an increase in renal excretory and haemodynamic function in response to intrarenally confined doses of the renin inhibitor ACRIP to inhibit renin, teprotide to inhibit the angiotensin converting enzyme (ACE) and saralasin to block Ang II receptors. We studied the effects of combined intrarenal blockade of the renin-angiotensin system in five female uninephrectomized conscious dogs on a sodium metabolic balance of 5 mmol/day. We infused ACRIP, teprotide and saralasin combined over 30 min in doses confined to the kidney, and again with an intrarenally confined dose of Ang II. There were no changes in renal function during the control study. During the combined infusion (ACRIP + teprotide + saralasin), the urine flow rate increased from 0.4 +/- 0.1 to 0.9 +/- 0.1 ml/min (P less than 0.001), urinary sodium excretion increased from 6.4 +/- 0.4 to 30.2 +/- 2.5 mumol/min (P less than 0.0001), the glomerular filtration rate increased from 29.3 +/- 0.7 to 42.0 +/- 1.2 ml/min (P less than 0.0001), renal plasma flow increased from 60.3 +/- 0.8 to 139.6 +/- 1.8 ml/min (P less than 0.001) and the fractional sodium excretion increased from 0.1 +/- 0.01 to 0.5 +/- 0.04% (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1989

Angiotensinogen gene expression in 3T3-L1 cells.

It has previously been established that angiotensinogen mRNA is present in brown and white adipose tissue of the rat. To determine whether angiotensinogen gene expression is present in adipocytes as compared with other cell elements, we have examined angiotensinogen mRNA in 3T3-L1 cells. These cells undergo adipocyte differentiation when the culture reaches confluence. To accelerate the differentiation process, cells were treated with dexamethasone and isobutylmethylxanthine for 3 days. On the 7th day after drug treatment, RNA was extracted from cells and was examined for angiotensinogen mRNA using a full-length rat angiotensinogen cDNA. Angiotensinogen mRNA was readily detected in differentiated 3T3-L1 cells. To determine when the gene is expressed, a 7-day time course from day 0 (before drug treatment) to day 7 was examined for the presence of angiotensinogen mRNA. In addition, C2 cells, a clonal cell line that does not differentiate into adipocytes, were examined. Angiotensinogen mRNA was detected on days 2-7 after drug treatment in 3T3-L1 cells, with no detectable levels in untreated 3T3-C2 cells. When 3T3-C2 cells were subjected to the same drug regimen, angiotensinogen mRNA levels increased in the same time course as 3T3-L1 cells. However, the increase in angiotensinogen message was greater in differentiating 3T3-L1 cells than in the nondifferentiating 3T3-C2 cells. Thus angiotensinogen mRNA is present in both adipocytes and in fibroblast-like cells and appears to be regulated by steroids.

1-Methyl-3-isobutylxanthine↗

PubMed1989

Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule.

Dopamine is synthesized within the kidney and dopamine 1 (DA1) receptors are associated with the proximal tubule. In pharmacological doses, dopamine increases renal blood flow and sodium excretion. It is possible that dopamine formed intrarenally acts locally via renal dopamine receptors to control renal function. We investigated the possible paracrine action of renal dopamine by intrarenal administration of a specific DA1 antagonist, Sch 23390, in doses confined to the kidney in conscious uninephrectomized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Changes (mean +/- SE) in renal excretory and hemodynamic function in response to cumulative infusions of several doses of Sch 23390 (0.01, 0.1, 1.0, 5.0, and 10.0 pmol.kg-1.min-1) were studied. Sch 23390 at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or sodium excretion. Sch 23390 in doses from 0.1 to 10.0 mol.kg-1.min-1 caused a significant dose-dependent antidiuresis (F = 44.9, P less than 0.0001) and antinatriuresis (F = 42.1, P less than 0.0001) and a decrease in fractional sodium excretion (F = 44.2, P less than 0.0001). No changes in estimated renal plasma flow, glomerular filtration rate, plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure occurred with any dose of intrarenal Sch 23390 infused into the renal artery. Rebound diuresis and natriuresis occurred after cessation of the DA1 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Distribution of renin mRNA and its protein in the developing kidney.

The intrarenal distribution of renin changes markedly during maturation. To determine whether renin gene expression changes along the developing renal vasculature, renin mRNA distribution was assessed using in situ hybridization histochemistry. Fetal, newborn, and adult kidney tissue sections from Wistar-Kyoto rats were hybridized with an oligonucleotide complementary to rat renin mRNA. In fetal kidneys, renin mRNA was found in the vascular pole of juxtamedullary glomeruli and along afferent, interlobular, and arcuate arteries. In kidneys from newborn rats, renin mRNA localized throughout the whole length of afferent arterioles, but was not detected in interlobular or arcuate arteries. In adult kidneys, hybridization signals were less intense and confined to the juxtaglomerular apparatus. Immunolocalization of renin with a polyclonal anti-rat renin antibody paralleled closely the mRNA distribution. Northern blot analyses demonstrated that renin mRNA levels were higher in fetal and newborn (20- and 10-fold, respectively) than in adult kidneys. We conclude the following. 1) The fetal kidney expresses the renin gene. 2) Expression of the renin gene is subjected to developmental changes. 3) As maturation progresses, localization of renin synthesis and storage shifts from large intrarenal arteries to a restricted, classical juxtaglomerular site in the afferent arteriole.

Animals↗

PubMed1989

Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.

The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2 = 42 +/- 1 mm Hg) in the presence of indomethacin (2.8 x 10(-5) M). This moderate degree of hypoxia inhibited (p less than 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p less than 0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than in endothelium-denuded vessels (0.70 +/- 0.12 vs. 0.09 +/- 0.03 g, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1989

Probing of the canine mammary artery damages endothelium and impairs vasodilation resulting from prostacyclin and endothelium-derived relaxing factor.

It is routine practice for many cardiac surgeons to probe internal mammary arteries to dilate them before their use. The effects of such probing on endothelium integrity, prostacyclin production, and vasodilation resulting from endothelium-derived relaxing factor and from prostacyclin were investigated in vessels isolated from mongrel dogs. Dose-dependent relaxation responses of isolated segments of probed and unprobed mammary arteries to the endothelium-dependent vasodilators methacholine, calcium ionophore (A23187), and melittin were determined in both the presence and absence of indomethacin. Prostacyclin production by probed versus unprobed vascular segments was determined under basal and A23187-stimulated conditions by radioimmunoassay for 6-keto-prostaglandin F1 alpha, and endothelial integrity was determined by scanning electron microscopy. Scanning electron micrographs of segments revealed marked endothelial cell disruption in probed versus unprobed vessels. The dose-dependent relaxation responses to all drugs studied were significantly impaired (p less than 0.05) in probed versus unprobed vessels in both the presence and absence of indomethacin. In addition, prostacyclin release as measured by production of 6-keto-prostaglandin F1 alpha was significantly (p less than 0.05) impaired in probed versus unprobed vessels under both basal and A23187-stimulated conditions. These results imply that routine probing of the internal mammary artery may damage endothelium, impair prostacyclin production, and impair endothelium-dependent vasodilation resulting from both prostacyclin and endothelium-derived relaxing factor.

Animals↗

PubMed1988

Endothelium-derived relaxing factor release associated with increased endothelial cell inositol trisphosphate and intracellular calcium.

The release of eicosanoids and endothelium-derived relaxing factor (EDRF) from endothelial cells is thought to involve a calcium-dependent step. Using cultured bovine aortic endothelial cells as a model system, we have examined the relation between agonist-induced changes in inositol polyphosphates and calcium levels within the endothelial cells and extracellular calcium on EDRF release. In a superfusion-cascade system, EDRF was detected by the relaxation of a rabbit aortic ring without endothelium suspended beneath a column of cultured endothelial cells. Endothelial cell stimulation by bradykinin or melittin induced dose-dependent relaxation of the bioassay ring. In addition, bradykinin and melittin stimulated an increase in intracellular calcium concentration in fura-2 loaded endothelial cells and an increase in inositol 1,4,5-trisphosphate (Ins[1,4,5]P3) in cells prelabeled with 3H-myoinositol. Bradykinin stimulation produced transient increases in Ins(1,4,5)P3, fura-2 fluorescence and transient EDRF release. Melittin stimulation induced more prolonged release of EDRF from the endothelial cell column, which was correlated with sustained increases in the fura-2 signal and the level of Ins(1,4,5)P3. Omission of calcium from the cell superfusate attenuated, but did not eliminate, bradykinin-induced EDRF release and the calcium transient, whereas the melittin-induced responses were only slightly attenuated. Endothelial cells clearly demonstrate receptor-activation of phospholipase C and release of sequestered calcium from subcellular sites in response to Ins(1,4,5)P3. These results imply that EDRF release is correlated with increased intracellular calcium levels seen in the absence of extracellular calcium. However, sustained release of EDRF does require influx of extracellular calcium via an undefined mechanism.

Animals↗

PubMed1988

Cell and molecular studies of renin secretion.

Renin secretion has been studied in the past at the level of the whole kidney, but the control of the genetic basis of renin synthesis is poorly understood. We have studied the regulation of renin gene expression in the fetus and also in the adult rat in response to angiotensin converting enzyme (ACE) inhibition with enalapril in the presence and absence of angiotensin II (AII). In the fetus, vascular smooth muscle cells of the renal afferent arteriole and feeder vessels contain renin mRNA and immunostain for renin. With maturation, these vessels progressively lose the capacity to synthesize renin, and only the juxtaglomerular cells retain this capacity in the adult. However, in response to ACE inhibition, the adult renal feeder vessels acquire the capacity to synthesize and secrete renin within 7 days. This effect is partially reversed with co-administration of AII. In order to study renin biosynthesis and secretion at the cellular level, we have developed a new method of study of individual renin-secreting cells, the reverse hemolytic plaque assay (RHPA). Utilizing this method, we have demonstrated that ACE inhibition with enalapril increases the number of renin secreting cells by over 15-fold at physiologic calcium concentrations. Enalapril also induced a 3-fold increase in the amount of renin released as estimated by the area of the hemolytic plaques formed. Transmission electron microscopy (EM) of the renin-secreting cell at the center of a hemolytic plaque demonstrates modified vascular smooth muscle cells with cytoplasmic granules. In summary, ACE inhibition stimulates renin mRNA accumulation and redistributes renal renin content toward that observed in early fetal life. AII inhibits renal renin mRNA accumulation. ACE inhibition increases the number of renin secreting cells as well as the amount of renin secreted by each cell. The individual renin secreting cell is a modified vascular smooth muscle cell with cytoplasmic secretory granules. Further studies of the cellular pathways for renin secretion can be provided by EM immunocytochemistry of the individual renin secreting cell.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Use of cultured cells to study the relationship between arachidonic acid and endothelium-derived relaxing factor.

We have used mixed- and co-cultures of endothelial and vascular smooth muscle cells to investigate the role of phospholipase activation and arachidonic acid metabolites in the production of endothelium-derived relaxing factor (EDRF). Inhibition of phospholipase A2 with para-bromophenacyl bromide, dexamethasone or quinacrine, alone or in combination, blocked arachidonate release by 50%-60% but had no effect on EDRF production as assessed by cyclic GMP accumulation in mixed- or co-cultures of endothelial and vascular smooth muscle cells. Inhibition of the phospholipase C-diacylglycerol (DAG) lipase pathway of arachidonate release by the DAG lipase inhibitor RHC-80267 also caused partial inhibition of arachidonate release and had no effect on EDRF. When both phospholipase A2 and phospholipase C pathways for arachidonate mobilization were inhibited (dexamethasone + RHC 80267), arachidonate release was totally inhibited while EDRF release remained intact. We conclude that neither phospholipase activation nor arachidonate mobilization is required for EDRF release from cultured bovine endothelial cells.

Acetophenones↗

PubMed1988

Intrarenal dopamine acts at the dopamine-1 receptor to control renal function.

Exogenous dopamine increases renal blood flow and produces diuresis and natriuresis in mammalian species. Dopamine is produced intrarenally and dopamine-1 receptors have been demonstrated within the kidney. However, the role of intrarenal dopamine in the control of renal function is unknown. We studied the renal effects of a specific dopamine-1 antagonist, SCH 23390 (SCH, MW 398, Schering-Plough, Bloomfield, New Jersey, USA) infused into the renal artery of uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 40 mmol/day. The infusion of SCH at 0.01 pmol/kg per min did not change the urinary flow rate or urinary sodium excretion. Significant dose-dependent reductions in urine volume, urinary sodium excretion and fractional excretion of sodium were observed with intrarenal SCH administration at 0.1, 5.0 and 10 pmol/kg per min. Rebound diuresis and natriuresis occurred after cessation of SCH administration. There were no changes in renal haemodynamic function, systemic plasma renin activity (PRA), plasma aldosterone concentration or mean arterial pressure during intrarenal SCH administration. These results demonstrate for the first time that intrarenal dopamine controls renal function physiologically by acting at the renal dopamine-1 receptors.

Animals↗

PubMed1988

Development of a new fluorescent angiotensin II probe.

Angiotensin II (ANG II) was conjugated to polystyrene Latex fluorescent microspheres (0.5 or 0.05 micron diam) with carbodiimide. Biological activity of the ANG II-conjugated microspheres (ANG II microspheres) was assessed in dispersed hepatocytes. The 0.05 micron ANG II microspheres inhibited glucagon-stimulated adenosine 3',5'-cyclic monophosphate accumulation and stimulated phosphorylase activity in hepatocytes, whereas the 0.5 micron ANG II microspheres only stimulated phosphorylase activity. The biological activity of the ANG II microspheres was caused by the conjugated ANG II and not by "free" ANG II associated with the spheres or by trypsin-like activity of hepatocytes causing release of ANG II from the microspheres. Binding of 0.05 micron ANG II to hepatocytes was readily observed with fluorescence microscopy. Little, if any, binding was observed with microspheres without conjugated ANG II. This fluorescent preparation of ANG II may have great utility in the study of receptor behavior after binding in individual cells.

Angiotensin II↗

PubMed1988

Renin and angiotensinogen gene expression in maturing rat kidney.

To determine whether angiotensinogen (Ao) and renin are synthesized by the immature kidney and to assess the changes in intrarenal renin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and Ao relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and Ao cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I.h-1.mg protein-1 in the incubation media. RRC was higher in newborn than in adult SHR (979 +/- 164 vs. 206 +/- 47) and WKY (573 +/- 69 vs. 297 +/- 74) (P less than 0.05). In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animal. Ao mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and Ao genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

Aging↗

PubMed1988

Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition.

To define whether intrarenal renin and angiotensinogen synthesis and distribution are affected by angiotensin-converting enzyme (ACE) inhibition, a control group of adult, male Wistar-Kyoto rats (n = 7) was compared with a group of rats treated with enalapril (n = 8) for 5 days. Kidney renin and angiotensinogen mRNA levels were detected by Northern and dot blot analysis, using full-length rat renin and angiotensinogen cDNAs. Renin mRNA levels in the enalapril-treated group were 4.6-fold higher than in the control group (P less than 0.05). Angiotensinogen mRNA levels were not significantly different. The intrarenal distribution of renin assessed by immunocytochemistry was markedly different between the two groups of rats. Whereas in the control kidney renin was localized in a juxtaglomerular position, in the kidneys from enalapril-treated rats, renin immunoreactivity of the afferent arteriole extended well beyond the juxtaglomerular loci in the direction of the interlobular artery. The percent of afferent arteriolar length immunostained for renin was higher in the enalapril-treated (53 +/- 17%) than in the control (33 +/- 15) group. Similarly, the ratio of immunostained juxtaglomerular apparatuses (JGA) over total number of JGA and the ratio of immunostained arteries over total number of arteries were higher in the enalapril-treated (0.84 +/- 0.017; 0.68 +/- 0.03) than in the control (0.67 +/- 0.034; 0.43 +/- 0.045) group (P less than 0.05). We conclude that chronic ACE inhibition enhances intrarenal renin synthesis and increases renin expression upstream from the glomerulus and in new sites in blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗